The use of adamantane derivatives falling under the cited general formula I for the therapy of certain diseases is already known. Thus, for instance, the dopamine-related influence of amantadine (1-adamantanamine) is described in a series of publications. Also an antiviral effect of certain amino-adamantanes has been demonstrated. In addition, EP B1-392059 shows the use of adamantane derivatives in preventing and treating cerebral ischaemia. According to this publication adamantane derivatives having the formulua I as described above can protectively prevent destruction of brain cells following an ischaemia, the adamantane derivatives being employed as antagonists for the NDMA receptor channels of the nerve cells. In EP-B1-392059 both general and special methods of producing adamantane derivatives falling under the above-cited formula I are described.
The publication by Ehrenberger and Felix in Acta Otalarygnol (Stockholm) 1995; 115: 236-240 concerns neurotransmission between the inner hair cell of the inner ear and the afferent neuron. An attempt is made to explain certain illnesses of the inner ear in a model by a so-called glutamate neurotoxicity, it being indicated in this context to use antagonists which block the glutamate link of the postsynaptic membrane. It is in this context that it is also termed conceivable to use antagonists for the glycine link, the redoxmodulating location or for the NMDA receptor complex, for example an adamantane derivative. The quinoxaline derivate caroverine tested in the Ehrenberger and Felix publication fails to produce any satisfactory results in the treatment of tinnitus thought to be induced by a glutamate, however.
At the same time it is to be realized that diseases of the inner ear are widespread, especially as regards diseases or disturbances in which subjective noise in the ear, so-called tinnitus occurs. It is estimated that in Germany alone roughly 6 million people suffer from tinnitus. In roughly 800,000 cases the tinnitus is so pronounced that these patients need intensive treatment by a physician, due to the patient being seriously handicapped by tormenting ear noise. At this time no reliable therapy is available.
As regards the complexity of inner ear diseases, especially in the case of tinnitus which is still to be conclusively explained, a series of medicamentous therapies has been proposed hitherto. These include, in addition to the use of anaesthetica, for example the application of lidocaine-type antiarrhythmica or anticonvulsiva, e.g. carbamazepine. However, in most cases treatments of this kind fail to bring satisfactory results. In-patient infusion therapy with procaine appears to be the sole form of tinnitus therapy which is superior to a placebo, albeit only to a minor degree. Here too, the effect is only temporary, however.